OBJECTIVE: To introduce the methodology validation and quality control in bioanalytical procedures and its expected trend of development.METHODS: According to the bioanalytical validation reflected in FDA guidelines and other publications,based on the guidance of SFDA and the standard operating procedure of our phase I clinical trial lab,we summarized the procedure and questions of bioanalytical methodology validation.RESULTS: The methodology validation and quality control in bioanalytical procedures and the possible risks involved in the methodology validation were summarized.CONCLUSIONS: The established methodology validation in bioanalytical procedure and quality control contents were basically consummate,but the standards for the methodology validation should be formulated based on reality.

Primary gallbladder cancer is a relatively common biliarv malignant tumor but with a high mortality rate.Most patients with this disease reach an advanced stage when late onset symptoms occtur, and the prognosis tends to be poor even after radical operation.Searching for new diagnostic approaches of primary gallbladder, standardizing treatment strategy, conducting multieenter clinical trials of new drug, developing preventive measures according to different situations are significant methodls to improve the treatment effect prognosis.In this article, we reviewed the research progress of high risk factors, diagnostics, and treatment strategies of primary gallbladder cancer.

Objective To study the mechanisms of increasing amyloid [β1-42 (Aβ42) level by presenilin-1 (PS-1) mutation of V97L.Methods Expression level of neprilysin (NEP) in nontransfected, or mock vector, wild type (wt) PS-1 and V97L-PS-1-transfected SH-SY5Y cells were assessed by reverse transcriptional-polymerase chain reaction (RT-PCR) and Western blot.The level of Aβ42 was also assessed by enzyme linked immunosorbent assay (ELISA).Results The mRNA level of NEP was decreased significantly in PS-1 V97L transfected cells (0.650 ± 0.010) compared to that in normal cells (1.090 ± 0.015), wt PS-1 gene (1.040 ± 0.021) and mock (1.080 ± 0.020) stably transfected cell lines (t = 9.236, 10.452, 5.678; all P < 0.01).Although there was a decreased tendency in the protein expression of NEP in PS-Ⅰ V97L transfected cells (1.000 ± 0.126)compared to that in normal cells (1.020 ± 0.110), wt PS-1 gene (1.040 ±0.110), mock (2.130 ±0.130) stably transfected cell lines, nosignificant differences were found.The expression of Aβ42 was increased significantly in PS-1 V97L transfected cells compared to other cell lines (t = 2.109, 3.355, 3.976; all P < 0.01).Conclusions PS-1 V97L mutation can decrease the transcription of NEP, however, in contrast, this mutation also resulted in increased Aβ42.The mechanism needs further analysis.

[Objective]To explore the indications and operative techniques for comminuted fracture of proximal humerus. [Method] Twelve patients with fracture of proximal humerus were chosen, observation was made after locking proximal humerus plate fixation with anterior acromioplasty. [Result]The average follow-up period were 12 months (6～24months). All patients' fracture in surgery group had been union and all shoulder had good functions. No incidence of avascular necrosis and nonunion was found. [Conclusion]Rigid fixation of displaced comminuted fractures of proximal humerus with anterior acromioplasty is a simple and effective technique to prevent subacromial impingement syndrome after surgery. Precise osteotomy and early postoperative exercises are the key to success.

Objective To evaluate the effectiveness of Leprosy Elimination Compaigns (LEC) integrated with routine case- finding of leprosy in the high leprosy- epidemic areas in Yunnan, Guizhou and Sichuan Provinces. Methods Extensive health education of leprosy in the community, training of paramedical workers on leprosy, clue survey and contact survey were carried out to make diagnosis and provide treatment. Results A total of 122 new leprosy cases were detected in 6 high leprosy- epidemic counties through LEC in 1999 with a detection rate of 3.7/100 000, but in contrast, the annual number of newly detected leprosy cases was 67 cases with an average detection rate of 2/100 000 during the period of 3 years before LEC. Among the newly detected leprosy cases, about 47％ were leprosy household contacts. Conclusion LEC combined with routine activities of case finding can improve the detection of the back- log cases in the communities. In the high epidemic areas, especially in the remote and difficult- to- access areas, majority of leprosy cases can be detected through combining active and passive case- finding methods, providing extensive health education, improving leprosy services in skin clinic, leprosy contact and clue surveys.

The central of micturition and urinary continence in cats and humans is organized in similar manner. During the last decade, knowledge of neural pathways involved in micturition and continence has been greatly expanded. This review will summarize results from recent animal and human experiments.

Objective:To study Ca~(2 +) changes~( )in detrusor cell of the unstable bladder of rabbit~(,)s partial bladder outlet obstruction. Methods: Thirty male New Zealand White rabbits were divided into 2 groups randomly. In the experiment group the unstable bladder were confirmed by Urodynamics and the sham operated age-matched rabbits acted as the control group eight weeks after operetion. bladder smooth muscle cells were isolated by collagenase digestion. Intracellular Ca~(2+) levels in detrusor cell were observed by confocal laser scanning microscope (CLSM). Results: Intracellular Ca~(2+) concentration significantly increased in the experiment group (Ca~(2+) overload). Conclusion:It was a important pathogeny for the unstable bladder of partial bladder outlet obstruction that pathological changes of Ca~(2+) with the unstable bladder.

Considerable advances have been made in the understanding of the cellular processes that result in contraction and relaxation of detrusor smooth muscle recently,particularly in the role and modulation of calcium.Several changes in these cellular mechanisms that impair normal function have been observed in detrusor muscle from patients with unstable bladders.Whether these changes represent primary causes of bladder dysfunction or whether they are secondary to bladder dysfunction remains to be determined.Nevertheless,the identification of specific cellular lesions in bladder dysfunction presents a novel approach to identification of drug targets and potential treatment modalities.

To investigate the effects of freezing the area of first porta hepatis which involves Glisson duct system,16 pigs were randomly divided into 2 groups. Group A:structures of the first porta hepatis were frozen by a dish-like cryoprobe (D=3.0cm) with temporary blockage of hepatic portal blood during freezing,the temperature at the end of 1,2,3minutes of cryotherapy was -50℃,-110℃,-131℃.Group B:sham operation,only with hepatic portal blockage for 3 minutes. Liver function tests, 99mTc-EHIDA scintiscanning,and pathological observation were used to evaluate the effects of the cryosurgery postoperatively.The results showed that the bile duct systems on first porta hepatis were severely destroyed by the cryosurgery,the cryoimpairment of common bile duct and/or common hepatic duct led to complications of progressive, irreversible, cryptic necrosis, fistula and pyogenic angiocholitis. The large freezing necrotic lesion in the porta hepatis might compress the portal vein. The perfect protection of biliary system should be accomplished in the cryosurgery of the first porta hepatis to avoid severe complications.